The Effects of Omega-3 Fatty Acids on Aspirin Resistance

Although aspirin has been a stalwart treatment in the prevention and treatment of myocardial infarction and stroke, it does not have its expected effects in a significant proportion of the population. This phenomenon has been termed "aspirin resistance". Omega-3 fatty acid supplementation has been associated with a reduced risk of sudden cardiac death and myocardial infarction. The beneficial effects of omega-3s are considered to be partially due to their ability to prevent platelet aggregation. However, the ability of omega-3s to enhance the effects of aspirin in those who suffer from aspirin resistance has not been determined. It is known that aspirin stimulates the production of potent lipid mediators from omega-3 fatty acids and that these mediators have powerful antiinflammatory and tissue-protective effects. Thus, the treatment of individuals at high risk for myocardial infarction and stroke with both aspirin and a pharmaceutical-grade omega-3 fatty acid medication may be a powerful combination in the prevention and treatment of life-threatening cardiovascular disease.

Study Protocol: Non-smoking male and female subjects between the ages of 18 and 50 not taking any medications, vitamin pills, nutritional supplements, or herbal preparations were recruited. Subjects with a history of chronic diseases (e.g. cardiovascular, renal, hepatic, neurodegenerative, neoplastic, metabolic {diabetes}, hypertension; based on screening medical history, a complete blood count, and comprehensive metabolic profile), or allergic reactions to aspirin, fish, fish oils, or non-steroidal anti-inflammatory drugs were excluded. Other exclusions included drinking more than three alcoholic beverages a day, or having any of the following conditions: an ulcer or bleeding in the stomach, liver or kidney disease, bleeding or blood clotting disorder (e.g. hemophilia), congestive heart failure, fluid retention, high blood pressure, gout, asthma, arthritis, or nasal polyps. This was a randomized, placebo-controlled, double-blinded trial with a cross-over design. Each subject served as his/her own control. The study involved four visits four weeks apart, all hosted in the University of Rochester Clinical Research Center. At each separate study visit, each subject received (using a randomized protocol) placebo, 81 mg aspirin, 4 g Lovaza(R)(3.4g of EPA+DHA), or both aspirin and Lovaza(R). Thus, each subject received each of these treatments individually in a random fashion over the four visits. Subjects, Center staff, and investigators were blinded as to which treatment was given at each visit and this ensured by the study pharmacist making the tablets and capsules for each treatment appear identical. Prior to each visit, subjects ate a standard low-fat dinner the prior evening, then fasted for at least 8 hours prior to arrival at the Center. Subjects were required to abstain from taking aspirin or non-steroidal anti-inflammatory drugs for 10 days prior to each visit and omega-3 fatty acids for 30 days prior to the baseline study visit, and all subsequent clinic visits. Visits lasted approximately 6 hours, with subjects at bedrest. A venous catheter was placed in a peripheral vein (saline lock, 18 gauge or larger, {no heparin used} in the forearm) with blood drawn, at baseline and 4 hours post-treatment, into citrated tubes at each visit for Platelet Function Analyzer-100 (PFA-100-Siemens, Deerfield, IL) closure time testing. Subjects were provided with a standard low-fat breakfast after the baseline phlebotomy.

Inclusion criteria

• Willing to participate by providing informed consent and committing to complete the study. This includes adhering to the study diet.
• No chronic disease by history and based on a complete blood count and comprehensive metabolic profile.
• Commitment to not taking aspirin, non-steroidal anti-inflammatory medications, and to limit fish intake to ≤2 meals during the 7 days prior to each CRC study period. They will also need to abstain from taking a list of over-the-counter medications that include aspirin. For the duration of the study, they will also be asked to abstain from taking fish and flax seed oil supplements.

Exclusion criteria

• Reports the presence of chronic disease (e.g. cardiovascular, renal, hepatic, neurodegenerative, neoplastic, metabolic {diabetes}, hypertension).
• Reports taking a systemic medication chronically.
• History of serious adverse reaction or allergy to aspirin or fish oil.
• Baseline platelet count <100 000 or >500 000, hematocrit <30%, or white blood cell count >20 000.
• Any abnormality from a screening CBC and complete blood count that suggests acute or chronic disease.
• Nicotine user.
• History of alcohol abuse
• Pregnancy by history or urine/serum pregnancy test
• History of intestinal malabsorption syndrome including gastric bypass surgery